Quantitative characterization of tissue structure and function is one of the most challenging problems in Medical Imaging. Field of view, depth of interrogation, and resolution are critical features that dramatically impact image quality and information content. To this end, we propose to advance the development of a new imaging technique known as Modulated Imaging (MI) and to assess the viability of this as a clinical device that will provide objective parameters that can be used to determine status of in-vivo tissue. Modulated Imaging employs patterned illumination to non-invasively obtain subsurface images of biological tissues. This non-contact approach enables rapid quantitative determination of the optical properties of tissues over a wide field-of-view. When combined with multi-spectral imaging, the optical properties at several wavelengths can be used to quantitatively determine the in-vivo concentrations of chromophores that are relevant to flap health, namely, oxy- and deoxy-hemoglobin. Furthermore, images at various spatial frequencies can be processed to visualize subsurface features in terms of scattering and absorption. Once optimized for a particular application, MI can be executed using consumer grade electronics such as those currently employed in digital cameras and DLP projectors. Hence, it is plausible to consider the potential for Modulated Imaging to be executed as a relatively inexpensive medical device. The broad goal of this proposal is to develop a robust, user-friendly MI platform capable of quantitative imaging appropriate for deployment at clinical sites. It will possess sufficient spatio-temporal resolution to study both fast (i.e., ms timescale) and localized (i.e., hundreds of m to mm) events at depths of several millimeters in tissues. This will enable quantitative insight into disease progression and therapeutic response in areas such as wound healing, dermatology, skin cancer and reconstructive surgery. To achieve this, we propose to design and fabricate a platform instrument based on Modulated Imaging (MI), a technology that has been developed over the course of the most recent Laser and Medical Microbeam Program (LAMMP;a NIH/NCRR Biomedical Technology Resource Center) funding period. The proposed research will following a methodical development plan including the following steps: 1) Design and fabrication of a standardized Modulated Imaging platform for human subject measurements, 2) Design and development of a turnkey software interface for clinical use, 3) Validation of the MI device performance in a laboratory setting and 4) Deployment of the MI device clinically for real-world testing and evaluation. Leveraging existing IRB approved clinical protocols and ongoing LAMMP- related studies, we will perform feasibility studies for skin-related applications, including normal skin, port-wine stain, melanoma, and skin flap surgeries. Upon successful completion of the Phase I research outlined herein, we intend to pursue a Phase II proposal that will involve fabrication and deployment of multiple devices. Ultimately, our intent is to methodically develop Modulated Imaging as a commercially viable medical device. PUBLIC HEALTH RELEVANCE: We propose to develop a robust imaging platform for quantitative imaging of subsurface tissue properties for clinical imaging applications. This system will implement Modulated Imaging (MI) technology, a non-contact imaging method developed under the Laser Microbeam and Medical Program center at the Beckman Laser Institute, UC Irvine. By accurately knowing what areas of tissue are healthy during surgery or in the Intensive Care Units (ICU), doctors may intervene and perform more timely procedures to avoid permanent tissue damage. Benefits include margin identification of skin cancer lesions, reducing unnecessary wound care procedures such as amputations in diabetic and trauma patients, and skin grafting in burn patients. Economically, the Modulated Imaging device will reduce hospital costs by eliminating unnecessary additional hospital days for these patients.